1. Field of the Invention
The present invention relates to a microchip useful as a μ-TAS (Micro Total Analysis System) used for environmental analysis, chemical synthesis and biochemical examination of DNA, protein, cells, blood and the like. The present invention is also related to a method of manufacturing a microchip.
2. Description of the Background Art
Recently, in the field of medical, health, food and drug discovery, importance of sensing, detecting and determining quantity of chemical substance and biological matter such as DNA (Deoxyribo Nucleic Acid), enzyme, antigen, antibody, protein, viruses and cells has been increasing, and various biochips and micro chemical chips (hereinafter generally referred to as microchips) allowing measurement of these have been proposed.
A microchip has a fluid circuit therein, and the fluid circuit mainly consists of various sections including a liquid reagent holding section holding liquid reagent for processing a specimen as the object of examination/analysis (such as blood) or for causing a reaction with the specimen, a mixing section for mixing the specimen with the liquid reagent and a detecting section for analyzing and/or examining the resulting mixture, and fine fluid paths (for example, having the width of a few hundred μm) appropriately connecting these sections to each other.
The microchip having such a fluid circuit enables a series of experiments/analysis operations, which has been conducted in a laboratory, within a chip having the size of a few centimeters square and the thickness of a few millimeters. Therefore, it is advantageous in many aspects. For example, it requires small amount of specimen and reagent, its cost is low, reaction speed is fast and hence examination with high throughput is possible, and the result of examination can be provided at the site where the specimen is taken. The microchip as such has been suitably used, for example, for biochemical examination such as blood test.
Generally, a microchip is fabricated by joining a first plastic substrate having a recess (trench) forming the fluid circuit and a second plastic substrate not having any recess on its surface, such that the fluid circuit is formed in the microchip. Here, in order to improve controllability of liquid moving through the fluid circuit and to prevent the liquid from adhering and remaining on the inner wall of fluid circuit, sometimes that surface of the first plastic substrate which has the recess (trench) formed thereon is subjected to water-repellant finishing, by applying a coating agent or the like in advance.
Here, in continuous production of microchips, when surface processing agent such as the coating agent is applied to the substrate surface, it is preferred to have a step of confirming, substrate by substrate, whether or not the surface processing agent has been reliably applied to the substrate surface. This is to prevent the risk that an ejecting portion of an applicator used for applying the surface processing agent clogs during continuous production and the surface processing agent is not actually applied.
Japanese Patent Laying-Open Nos. 2003-145028, 2001-153803, 08-141487, 07-24391 and 05-331438 disclose methods of inspecting state of application of liquid material such as a coating agent or adhesive agent. According to the methods, fluorescent dye is introduced to the liquid material, the surface to which the liquid material has been applied is irradiated with ultraviolet ray, and fluorescence emitted by the fluorescent dye in the liquid material is detected, to inspect the state of application of the liquid material. It is common in biochemical examination or environmental analysis using microchips that the reactant prepared in the microchip is analyzed at a detecting section of the microchip using optical measurement. Here, the detection light beam is directed to the detecting section of the microchip, and the transmitted or reflected light is detected. It is often the case that the detection light involves ultraviolet ray. If the detection light involves ultraviolet ray and the coating agent containing fluorescent dye has been applied to the inner wall of fluid circuit, fluorescence as a disturbance would generate when irradiated with the detection light beam. This hinders accurate optical measurement.
Further, an additive such as the fluorescent dye mentioned above may possibly hinder reaction between the specimen and the reagent for test in the microchip, or it may possibly be eluted to the reagent for test or to the mixture of specimen and reagent, making it difficult to attain highly accurate measurement. Therefore, in a microchip to be subjected to optical measurement and the like, a surface processing agent containing an additive such as a fluorescent dye cannot be used.